Brain metastasis is the most common intracranial tumor, occurring in 15-40% of all cancer patients with metastatic disease [1,2,3]. The incidence of brain metastasis has increased in recent years, possibly due to prolonged survival of cancer patients receiving aggressive treatments for their primary or systemic disease [1,2,3]. Given their overall frequency in the population, lung and breast cancer are by far the most common tumors to develop brain metastases [1,2,3].
Epidemiological studies suggest that brain metastases occur with a frequency of approximately 10-16% in patients with breast cancer, although large autopsy studies indicate that frequencies may be as high as 18-30% [2,3,4,5]. Brain metastases occur rapidly, usually within 2-3 years following diagnosis of systemic metastatic disease, and the median survival once there is brain involvement is a stifling 13 months with fewer than 2% of patients surviving greater than 2 years. Breast cancer involving the brain (parenchyma or leptomeninges) is considered a feature of late-stage progressive disease for which few effective treatments exist. Due to limitations imposed by the blood brain barrier (BBB), chemotherapy has not generally been used to treat most epithelial cancers that metastasize to the brain. Whole brain radiation can provide a survival benefit of 4-5 months, which can be further extended with stereotactic radiosurgery (SRS). Surgery can also lead to dramatic improvements in survival if fewer than 3 metastases exist and all are treated aggressively with surgery or SRS.
Currently there are few predictive measures for identification of patients at risk for developing brain metastasis from their primary cancer. In general, the development of brain metastases from breast cancer depends on several prognostic factors, including younger age, ethnicity, hormone receptor negative status, presence of BRCA1 germ-line mutations and the expression of the epidermal growth factor receptor 2 (Her2/neu) proto-oncogene, all of which contribute to an increased rate of brain metastasis [2].
There is a need to identify genomic and epigenomic biomarkers in breast cancer brain metastases to understand the landscape of breast cancer brain metastatic lesions. These biomarkers would allow for earlier diagnosis of breast cancer brain metastases and the development of new therapeutic targets to control this fatal manifestation of breast cancer.